Polymer mediated protein crystallisation

Nikolaidi, Dimitra (2013) Polymer mediated protein crystallisation. MPhil thesis, University of Nottingham.

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Abstract

Structure elucidation of a macromolecule can lead to the determination of its function. In the case of proteins, knowledge of their three-dimensional structure can be utilised in the identification of active site(s) and consequently in rational drug design. Commonly, X-ray crystallography is implemented on a high quality single crystal of the target macromolecule, in order to elucidate its structure. Moreover, crystallised protein molecules may remain active which can then be used in controlled drug delivery. Unfortunately, the successful crystallisation of a macromolecule can be seen as the most challenging aspect in this endeavour, given that predicting, screening and directing crystallisation remains an elusive goal.

A possible solution to this problem is the use of heterogeneous nucleation, where a foreign surface is employed to lower the energy barrier for nucleation to occur. Heteronucleation has been utilised in the crystallisation of small organic molecules, inorganic complexes, extended networks and proteins. Polymeric surfaces, as heteronucleants, in protein crystallisation have been known to increase nucleation density rates and selectively crystallise particular forms of proteins. Moreover, imprinted polymeric surfaces have been successfully used to selectively crystallise inorganic molecules as well as a small range of well studied proteins.

This thesis presents the effects of polymers on the crystallisation of two proteins, that of mutant human thioredoxin and wild-type hen egg-white lysozyme (HEWL). Polymers were used in solution, as physically adsorbed films as well as plasma polymers. Shape and size of the protein crystals was altered, while polymorphism was also achieved, in the presence of polymers with various functionalities. This work is a step towards the use of polymers as heteronucleants in directing protein crystallisation.

Item Type: Thesis (University of Nottingham only) (MPhil)
Supervisors: Alexander, C.
Subjects: Q Science > QD Chemistry > QD241 Organic chemistry
Q Science > QD Chemistry > QD901 Crystallography
Faculties/Schools: UK Campuses > Faculty of Science > School of Pharmacy
Item ID: 13192
Depositing User: EP, Services
Date Deposited: 18 Oct 2013 09:56
Last Modified: 01 Oct 2016 07:18
URI: http://eprints.nottingham.ac.uk/id/eprint/13192

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